The past and future of the human genome project

Double helix with a twist

Rarely has one project held such promise. Knowledge about the effects
of DNA variations among individuals may help researchers better
diagnose, treat and possibly eradicate the more than 4,000 genetically
inherited human disorders.

Los Alamos became interested in genetics early in the Lab’s history. The
Lab established health research units because radiation was known to
cause cell injury and genetic mutation. Researchers conducted early
biological research on whole animals to understand better the physio-
logic and genetic consequences of radiation exposure and to set rational
dose limitations for workers. In the 1960s, as this knowledge base
expanded, studies became increasingly sophisticated and included
investigations at the cellular and subcellular levels.

By the 1970s, Lab scientists were recognized world leaders in the area of
cell biology, especially in the development of instruments that could
rapidly measure the volume of each cell in a large cell population.
Researchers further refined those instruments, called flow cytometers, to
detect fluorescence emitted by stained cells. These instruments later
were used to analyze chromosomes as well as whole cells.

In the 1980s, the flow-cytometry resources at Los Alamos combined with newly developed recombinant-DNA
technology to construct a series of DNA libraries that represented the DNA in each of the human chromosomes. These
libraries were used with other laboratories throughout the world; they provided a means of rapidly mapping the
locations of human genes. It was also during this period that a group of Lab researchers created a national repository to
store DNA sequence information. The repository was called GenBank and is now maintained by the NIH.

The Los Alamos Center for Human Genome Studies —established in 1988 —better organized the effort to map and
sequence the human genome and make these data available to the research community. The Lab’s program became part
of the international Human Genome Project in 1990.

One of the Lab’s biggest accomplishments in genome research was the construction of the first high-resolution physical
map of human chromosome 16. Genes on chromosome 16 include those associated with leukemia, breast cancer,
prostate cancer, Batten disease, hemoglobin disorders and a type of kidney disease.

In 1996 Los Alamos joined forces with Lawrence Livermore and Lawrence Berkeley national laboratories to form the
Department of Energy’s Joint Genome Institute (JGI), combining the genome centers of each lab into one virtual
organization. The JGI is part of a consortium of five genome institutes that worked together to sequence the entire
human genome.

In June 2000, the announcement was made that the human genome had been sequenced. Scientists and historians have
compared unraveling the three billion or so base pairs to science and engineering accomplishments such as landing on
the moon and splitting the atom.

The sequence of the human genome is a draft sequence; gaps in the sequence remain, but esearchers are confident that
the draft will develop into a medical revolution.

All remaining gaps in the human genome sequence need to be filled. The Los Alamos Genome Center will close gaps in
the chromosome 16 sequence during the coming year. And still other mysteries need to be uncovered, such as the first
complete set of RNA molecules produced by the genome or the structural determination of the complement of proteins
encoded by the genome. Other milestones include eventually determining which genes are turned on and in what order
and how gene products interact with each other to determine how bio-molecular networks function. The Genome
Center will evolve from the role it has been playing in mapping and sequencing to playing a role in the determination of
how genomes use the information they encode to produce the molecules necessary to sustain life.

The Department of Energy's Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time.